Despite the demonstrated evidence-based efficacy of spinal manipulative therapy (SMT) and in particular, high velocity low-amplitude (HVLA) thrust technique, for the treatment of patients with acute lower back pain, multiple studies have demonstrated that HVLA-SMT is not typically recommended by primary healthcare providers. An important barrier to the translation of knowledge concerning HVLA-SMT and to the wider-spread utilization of this treatment for patients with acute spinal pain is the lack of a validated biological mechanism of action for HVLA-SMT. This pilot study will assess the feasibility of carrying out a larger multicentre study on the biological effects of HVLA-SMT in patients with an underlying acute inflammatory spine complaint. The larger study will be an in vivo randomized controlled trial (RCT) and nested cohort study of the effect of HVAL-SMT on cytokine expression in patients with acute sciatica secondary to lumbar disc herniation (AS-LDH). The objectives of the current study include: 1) To determine the rate of recruitment of AS-LDH patients willing to undergo a three- week course of HVLA-SMT while awaiting surgery; 2) To estimate important parameters that would inform sample size calculations for a larger study, including the rate of wait-listed patients actually avoiding surgery (due to recovery while waiting), the prevalence of cytokine mRNA expression in disc homogenate, and point estimates and standard deviations of cytokine levels in serum samples as well as periradicular and disc lavagate from surgically treated manipulated and non-manipulated patients; and 3) To describe the extent to which levels of biochemical inflammatory mediators at the time of surgery are associated with pre-surgical quality of life in manipulated versus non-manipulated patients. Thirty patients with AS-LDH on the waiting list for surgical lumbar discectomy with an identified date of surgery will be randomized to either four weeks of pre-surgical SMT or to a wait-list only control group. Serum cytokine measurements will be obtained from all patients at study enrolment, then at four weeks and at one day prior to the date of scheduled surgery; and at 12 and 24 weeks after the date of scheduled surgery. Additionally, mRNA cytokine expression will be measured in periradicular and disc lavagate, and disc homogenate harvested during surgery. Descriptive statistics for feasibility outcomes (including recruitment rate at each centre, point and range estimates of serum levels of different cytokines, and rates of cytokine expression and avoidance of surgery in manipulated and non-manipulated groups) will be reported and used to inform our final protocol for a larger study. This information will also help to inform the design f other future studies on the putative biological mechanisms of HVLA-SMT, particularly in the treatment of patients with acute sciatica from lumbar disc herniation. PUBLIC HEALTH RELEVANCE: Low back pain is a prevalent and burdensome problem in Western society. Spinal manipulation, although recommended in many scientific guidelines for acute lumbosacral pain, is under-utilized due to ongoing uncertainty regarding a specific biological effect and mechanism of action. This proposed study and subsequent larger multicentre trial seek to determine if spinal manipulation has a specific effect on biochemical inflammatory mediators, as well as corresponding clinical outcomes, in patients with a common, acute inflammatory spine condition, acute sciatica secondary to lumbar disc herniation.